Interpretive Summary: Sheep are the reservoir for ovine herpesvirus 2 (OvHV-2), the causative agent for sheep-associated malignant catarrhal fever (MCF). The disease primarily affects several ruminant species such as cattle, bison and deer, characterized by high fever, inflammation, ulceration, and exudation of the oral and upper respiratory mucous membranes, and sometimes eye lesions and nervous system disturbances. Virtually all sheep are subclinically infected with the virus under natural flock conditions and serve the source for viral transmission. Spontaneous cases of MCF-like disease in sheep have been suspected but never confirmed. In this study, MCF-like disease was induced experimentally in three sheep following aerosol transmission. Each of three OvHV-2 negative sheep was nebulized with 2 ml of nasal secretions containing approximately 3.7 x 109 OvHV-2 DNA copies from a sheep experiencing an intensive viral shedding episode. OvHV-2 DNA became detectable by PCR in the peripheral blood leukocytes of all sheep within 3 days post-aerosolization (PA), and animals seroconverted between 6 and 8 days PA. The sheep developed clinical signs with severe nasal discharges and fever at 14 days PA. One of three clinically affected sheep was euthanized at 18 day PA. The major lesions at necropsy were multifocal linear erosions and ulcers in mucosa of the cheeks, tongue, pharynx, and proximal esophagus, and mild disseminated pneumonia. Microscopically, there was extensive moderate superficial histiocytic lymphocytic rhinitis, with epithelial hyperplasia, disorganization, and degeneration. Moderate multifocal histiocytic bronchointerstitial pneumonia was associated with loss of terminal bronchiolar epithelium. Vasculitis was present only in the lung. The study revealed that clinical signs and lesions resembling MCF can develop when uninfected sheep are exposed to a high dose of the virus.

Technical Abstract:
Sheep are the reservoir for ovine herpesvirus 2 (OvHV-2), the causative agent for sheep-associated malignant catarrhal fever (MCF). The disease primarily affects several ruminant species such as cattle, bison and deer, characterized by high fever, inflammation, ulceration, and exudation of the oral and upper respiratory mucous membranes, and sometimes eye lesions and nervous system disturbances. Virtually all sheep are subclinically infected with the virus under natural flock conditions and serve the source for viral transmission. Spontaneous cases of MCF-like disease in sheep have been suspected but never confirmed. In this study, MCF-like disease was induced experimentally in three sheep following aerosol transmission. Each of three OvHV-2 negative sheep was nebulized with 2 ml of nasal secretions containing approximately 3.7 x 109 OvHV-2 DNA copies from a sheep experiencing an intensive viral shedding episode. OvHV-2 DNA became detectable by PCR in the peripheral blood leukocytes of all sheep within 3 days post-aerosolization (PA), and animals seroconverted between 6 and 8 days PA. The sheep developed clinical signs with severe nasal discharges and fever at 14 days PA. One of three clinically affected sheep was euthanized at 18 day PA. The major lesions at necropsy were multifocal linear erosions and ulcers in mucosa of the cheeks, tongue, pharynx, and proximal esophagus, and mild disseminated pneumonia. Microscopically, there was extensive moderate superficial histiocytic lymphocytic rhinitis, with epithelial hyperplasia, disorganization, and degeneration. Moderate multifocal histiocytic bronchointerstitial pneumonia was associated with loss of terminal bronchiolar epithelium. Vasculitis was present only in the lung. The study revealed that clinical signs and lesions resembling MCF can develop when uninfected sheep are exposed to a high dose of the virus.